Entrectinib in the treatment of ROS1-positive lung cancer

Abstract

The possibilities in the treatment of patients with non–small cell lung cancer are constantly expanding – thanks to high-performance genomic profiling methods, we are discovering new targets in the tumor for drug action, as a result, new targeted drugs appear, some of them have several application points. Multipurpose drugs have a number of advantages and therefore have become the main direction of drug development. Entrectinib is an oral low molecular weight multikinase inhibitor that blocks three targets at once – the receptors of tyrosine kinases ROS1, NTRK1/2/3 and ALK, in 2023 was approved by the Ministry of Health of the Russian Federation for the treatment of adult patients with ROS1-positive metastatic non-small cell lung cancer. This form of lung cancer is classified as a rare orphan disease, which usually occurs in younger people (about 50 years old), more often in women and non-smokers. Until recently , we had the only active targeted drug – crizotinib. It provided a sufficiently high immediate effect and long-term control of the disease. However, his intracranial activity was not evaluated prospectively, and a retrospective analysis showed modest results. Entrectinib is distinguished from its competitor by high intracranial activity, and, as is known, metastatic brain damage in patients with activating mutations is quite common. With comparable indicators of objective response, its duration and time to progression, entrectinib provides a high level of intracranial control and reduces the risks of progression in the central nervous system in patients who did not have brain metastases at the beginning of therapy. In addition, entrectinib demonstrates good tolerability.